The transcription factor lymphoid enhancer factor 1 controls invariant natural killer T cell expansion and Th2-type effector differentiation.
Bottom Line: These cells acquire multiple effector fates during their thymic development that parallel those of CD4(+) T helper cells.LEF1 also directly augments expression of the effector fate-specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ.Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.
Affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.Show MeSH
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Mentions: We questioned whether LEF1 deficiency was affecting the expression of TCF1 in iNKT cells because TCF1 is essential for CD4+ Th2 cell differentiation and ILC2 development and is generally redundant with or dominant to LEF1. TCF1 was expressed in all iNKT cells, and LEF1 expression was directly correlated with TCF1 in a subset of these cells (Fig. 7 A). Like LEF1, TCF1 was expressed most highly in ST1 and ST2 iNKT cells (Fig. 7 B); however, TCF1 was expressed in both CD4+ and DN iNKT cells and in ST3 iNKT cells (Fig. 7, B and C). Consistent with this expression pattern, TCF1 was expressed in iNKT2 and iNKT17 cells at levels comparable with cCD4+ T cells and at lower levels in iNKT1 cells (Fig. 7 B). Importantly, TCF1 was expressed equally well in control and Lef1Δ/Δ ST1 and ST2 iNKT cells, indicating that the alterations in iNKT cell development caused by LEF1 deficiency were not a consequence of a loss of TCF1 (Fig. 7 D). TCF1 expression was increased slightly in Lef1Δ/Δ ST3 iNKT cells, suggesting that there may be a selection for TCF1 in these cells or their progenitors when LEF1 is absent (Fig. 7 D). Therefore, our data revealed critical functions for LEF1 in iNKT cell expansion and the development of iNKT2 cells that were not compensated for by TCF1 despite TCF1 expression in all iNKT cells.
Affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.